Derbyshire, M. | bioRxiv Science

bioRxiv2022

Tbx3 is required for mammalian retinal angiogenesis.

PurposeIn Retinopathy of Prematurity (ROP), infants often have incomplete vascularization, affecting the temporal region. A factor expressed in this region during retinal development is the T-box factor, Tbx3, which has not been studied in the mammalian eye. The purpose of this study was to determine if Tbx3 is required during eye formation for retinal angiogenesis. MethodsConditional removal of Tbx3 from both retinal progenitors and astrocytes was done using the optic cup-Cre recombinase driver, BAC-Dkk3-CRE and analyzed using standard immunohistochemical techniques. ResultsWith Tbx3 loss, the retinas were hypovascular, as seen in patients with ROP and Familial Exudative Vitreoretinopathy (FEVR). Retinal vasculature failed to form the stereotypic tri-layered plexus in the dorsal-temporal region. Astrocyte precursors were reduced in number and failed to form a lattice at the dorsal-temporal edge. We next examined retinal ganglion cells, as they have been shown to play a critical role in retinal angiogenesis. We found that melanopsin expression and Islet1/2-positive retinal ganglion cells were reduced in the dorsal half of the retina. In previous studies, loss of melanopsin has been linked to hyaloid artery persistence, which we also observed in the Tbx3 cKO retina, as well as in infants with ROP or FEVR. ConclusionsTogether, these results show that TBX3 is required for normal mammalian eye formation for the first time. This potentially provides a new genetic model for retinal hypovascular diseases.

neuroscience↗

bioRxiv2018

Selective sweeps in populations of the broad host range plant pathogenic fungus Sclerotinia sclerotiorum

The pathogenic fungus Sclerotinia sclerotiorum infects over 600 species of plant. It is present in numerous environments throughout the world and causes significant damage to many agricultural crops. Fragmentation and lack of gene flow between populations may lead to population sub-structure. Within discrete recombining populations, positive selection may lead to a selective sweep. This is characterised by an increase in frequency of a favourable allele leading to reduction in genotypic diversity in a localised genomic region due to the phenomenon of genetic hitchhiking.\n\nWe aimed to assess whether isolates of S. sclerotiorum from around the world formed genotypic clusters associated with geographical origin and to determine whether signatures of population-specific positive selection could be detected. To do this, we sequenced the genomes of 25 isolates of S. sclerotiorum collected from four different continents - Australia, Africa (north and south), Europe and North America (Canada and the northen United States) and conducted SNP based analyses of population structure and selective sweeps.\n\nAmong the 25 isolates, there was evidence for four population clusters. One of these consisted of 11 isolates from Canada, the USA and France (population 1), another consisted of five isolates from Australia and one from Morocco (population 2). A further cluster was made up of Australian isolates, and the single South African isolate appeared to be from a separate population. We found that there was evidence of distinct selective sweeps between population 1 and population 2. Many of these sweeps overlapped genes involved in transcriptional regulation, such as transcription factors. It is possible that distinct populations of S. sclerotiorum from differing global environments have undergone selective sweeps at different genomic loci. This study lays the foundation for further work into investigation of the differing selective pressures that S. sclerotiorum populations are subjected to on a global scale.

genetics↗